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Biomedical subjects

L J Brown

Publications and source records attributed to L J Brown.

At least 19 recordsLinked to original sources
PubMed2005

Factors influencing PCR detection of viruses in cerebrospinal fluid of patients with suspected CNS infections.

BACKGROUND: Polymerase chain reaction (PCR) is used to detect viruses in the cerebrospinal fluid (CSF) of patients with neurological disease. However, data to assist its use or interpretation are limited. OBJECTIVE: We investigated factors possibly influencing viral detection in CSF by PCR, which will also help clinicians interpret positive and negative results. METHODS: CSF from patients with was tested for human herpesviruses types 1-6, JC virus, enteroviruses, and Toxoplasma gondii. The likelihood of central nervous system (CNS) infection was classified as likely, possible, or unlikely. PCR findings in these categories were compared using single variable and logistic regression analysis. RESULTS: Of 787 samples tested, 97 (12%) were PCR positive for one or more viruses. Of episodes likely to be CNS viral infections, 30% were PCR positive compared to 5% categorised as unlikely. The most frequent positive findings were Epstein Barr virus (EBV), enteroviruses, and herpes simplex virus (HSV). Enteroviruses and HSV were found predominantly in the likely CNS viral infection group, whereas EBV was found mainly in the unlikely group. Positive PCR results were more likely when there were 3-14 days between symptom onset and lumbar puncture, and when CSF white cell count was abnormal, although a normal CSF did not exclude a viral infection. CONCLUSIONS: The diagnostic yield of PCR can be maximised by using sensitive assays to detect a range of pathogens in appropriately timed CSF samples. PCR results, in particular EBV, should be interpreted cautiously when symptoms cannot readily be attributed to the virus detected.

Adolescent↗
PubMed2001

Duplex Scorpion primers in SNP analysis and FRET applications.

Scorpions are fluorogenic PCR primers with a probe element attached at the 5'-end via a PCR stopper. They are used in real-time amplicon-specific detection of PCR products in homogeneous solution. Two different formats are possible, the 'stem-loop' format and the 'duplex' format. In both cases the probing mechanism is intramolecular. We have shown that duplex Scorpions are efficient probes in real-time PCR. They give a greater fluorescent signal than stem-loop Scorpions due to the vastly increased separation between fluorophore and quencher in the active form. We have demonstrated their use in allelic discrimination at the W1282X locus of the ABCC7 gene and shown that they can be used in assays where fluorescence resonance energy transfer is required.

DNA Primers↗
PubMed2001

Independent movement of the regulatory and catalytic domains of myosin heads revealed by phosphorescence anisotropy.

Inter- and intradomain flexibility of the myosin head was measured using phosphorescence anisotropy of selectively labeled parts of the molecule. Whole myosin and the myosin head, subfragment-1 (S1), were labeled with eosin-5-iodoacetamide on the catalytic domain (Cys 707) and on two sites on the regulatory domain (Cys 177 on the essential light chain and Cys 154 on the regulatory light chain). Phosphorescence anisotropy was measured in soluble S1 and myosin, with and without F-actin, as well as in synthetic myosin filaments. The anisotropy of the former were too low to observe differences in the domain mobilities, including when bound to actin. However, this was not the case in the myosin filament. The final anisotropy of the probe on the catalytic domain was 0.051, which increased for probes bound to the essential and regulatory light chains to 0.085 and 0.089, respectively. These differences can be expressed in terms of a "wobble in a cone" model, suggesting various amplitudes. The catalytic domain was least restricted, with a 51 +/- 5 degrees half-cone angle, whereas the essential and regulatory light chain amplitude was less than 29 degrees. These data demonstrate the presence of a point of flexibility between the catalytic and regulatory domains. The presence of the "hinge" between the catalytic and regulatory domains, with a rigid regulatory domain, is consistent with both the "swinging lever arm" and "Brownian ratchet" models of force generation. However, in the former case there is a postulated requirement for the hinge to stiffen to transmit the generated torque associated by nucleotide hydrolysis and actin binding.

Animals↗
PubMed2001

All-cause mortality in the Canterbury (New Zealand) insulin-treated Diabetic Registry population.

OBJECTIVE: To establish all-cause death rates and life expectancies of and risk factors for mortality in insulin-treated diabetic individuals living in Canterbury, New Zealand. RESEARCH DESIGN AND METHODS: Insulin-treated diabetic subjects (n = 1,008) on the Canterbury Diabetes Registry were tracked over 9 years, and their vital status was determined. Death rates were standardized using direct and indirect methods. Cox proportional hazard regression was used to model the effects of demographic and clinical covariates on survival time. RESULTS: At study entry, age ranged from 2.9 to 92.7 years, with mean 48.7 +/- 20.4 years; age at diagnosis was 0.2-88.9 years, mean 34.5 +/- 20.0 years; and duration of diabetes was 0.1-58.5 years, mean 14.0 +/- 10.6 years. There were 303 deaths in 7,372 person-years of follow-up with a standardized mortality ratio (SMR) of 2.6 (95% CI 2.4-3.0). Relative mortality was greatest for those aged 30-39 years (SMR 9.2 [4.8-16.2]). The death rate for the diabetic cohort standardized against the Segi world standard population was 16.2 per 1,000. Attained age, sex, and clinical subtype were significant predictors of mortality The SMR for subjects with type 1 diabetes and age at onset <30 years was 3.7 (CI 2.7-5.0), 2.2 (1.8-2.6) for those with onset > or =30 years, and 3.1 (2.5-3.7) for subjects suspected of having latent autoimmune diabetes in adulthood or insulin-treated type 2 diabetes. Life expectancy was reduced for both sexes at all ages. CONCLUSIONS: Mortality rates for insulin-treated diabetic individuals remain high, resulting in shortened life spans relative to the general population. Marked differences in mortality exist between clinical groups of subjects. Further research is needed to improve diabetes classification and to clarify differences in health outcomes.

Adolescent↗
PubMed2001

Dental work force strategies during a period of change and uncertainty.

Both supply and demand influence the ability of the dental work force to adequately and efficiently provide dental care to a U.S. population growing in size and diversity. Major changes are occurring on both sides of the dental care market. Among factors shaping the demand for dental care are changing disease patterns, shifting population demographics, the extent and features of third-party payment, and growth of the economy and the population. The capacity of the dental work force to provide care is influenced by enhancements of productivity and numbers of dental health personnel, as well as their demographic and practice characteristics. The full impact of these changes is difficult to predict. The dentist-to-population ratio does not reflect all the factors that must be considered to develop an effective dental work force policy. Nationally, the dental work force is likely to be adequate for the next several years, but regional work force imbalances appear to exist and may get worse. Against this backdrop of change and uncertainty, future dental work force strategies should strive for short-term responsiveness while avoiding long-term inflexibility. Trends in the work force must be continually monitored. Thorough analysis is required, and action should be taken when necessary.

Delivery of Health Care↗
PubMed2000

Functional analysis of two promoters for the human mitochondrial glycerol phosphate dehydrogenase gene.

Mitochondrial glycerol phosphate dehydrogenase (mGPD) is abundant in the normal pancreatic insulin cell, but its level is lowered 50% by diabetes. To evaluate mGPD expression, we cloned and characterized the 5'-flanking region of the human mGPD gene. The gene has two alternative first exons and two promoters. The downstream promoter (B) is 10 times more active than the upstream promoter (A) in insulin-secreting cells (INS-1) and HeLa cells. Promoter B has higher activity in INS-1 than in non-beta cells. Deletion and mutation analysis suggested that a NRF-2 binding site at -94 to -101 and an E2F binding site at -208 to -215 are important regulatory cis elements in promoter B. Gel mobility shift assays indicated that the -94 to -101 region binds the NRF-2 protein. When INS-1 cells were maintained in the presence of high glucose (25 mm) for 7 days, mGPD was the only 1 of 6 enzyme activities lowered (53%). mGPD promoter B activity was reduced by 60% in INS-1 cells by the high glucose, but in HepG2 cells and HeLa cells, promoter B activity was unchanged or slightly increased. Deletion analysis indicated the glucose responsiveness was distributed across the region from -340 to -260 in promoter B. The results indicate that mGPD gene transcription in the beta cell is regulated differently from other cells and that decreased mGPD promoter B transcription is at least in part the cause of the decreased beta cell mGPD levels in diabetes.

Base Sequence↗
PubMed2000

Endometrial protection from tamoxifen-stimulated changes by a levonorgestrel-releasing intrauterine system: a randomised controlled trial.

INTRODUCTION: Tamoxifen is currently the most commonly used adjuvant treatment for breast cancer, however, it frequently causes episodes of unscheduled uterine bleeding, which could be associated with proliferative changes of the endometrium, or even endometrial cancer. We aimed to assess whether a levonorgestrel intrauterine system could modulate the uterine responses to tamoxifen. We also aimed to assess women's tolerance of the screening procedures, the insertion, removal, and potential side-effects of the device. METHODS: We did a randomised controlled trial, in which postmenopausal women who had had at least 1 year of adjuvant tamoxifen treatment and who were undergoing regular follow-up for breast cancer were randomly assigned to either endometrial surveillance alone, or endometrial surveillance before and after insertion of the levonorgestrel intrauterine system for 12 months. We assessed tolerance of the surveillance procedures and the device with visual analogue scales. FINDINGS: Baseline assessment showed only benign uterine changes in all women (n=122). Hysteroscopic assessment indicated a uniform decidual response (confirmed histologically in 40 of 41 cases) in all women fitted with the intrauterine system; there were no new polyps in these women and 13% had fewer fibroids than in controls. Both screening procedures and device were well tolerated. There was an excess of bleeding in the women fitted with intrauterine systems but this resolved to a baseline similar to those receiving surveillance only. INTERPRETATION: The levonorgestrel-releasing intrauterine system had a protective action against the uterine effects of tamoxifen. The effectiveness of this device in preventing uterine changes in the endometrium needs to be assessed in the context of decreasing the need for repeated investigations of postmenopausal bleeding in women taking tamoxifen.

Aged↗
PubMed2000

Platelet-derived endothelial cell growth factor expression and angiogenesis in cervical intraepithelial neoplasia and squamous cell carcinoma of the cervix.

Growth and metastatic spread of invasive carcinoma depends on angiogenesis, the formation of new blood vessels. Platelet-derived endothelial cell growth factor (PD-ECGF) is an angiogenic growth factor for a number of solid tumors, including lung, bladder, colorectal, and renal cell cancer. Cervical intraepithelial neoplasia (CIN) is the precursor to squamous cell cervical carcinoma (SCC). Mean vessel density (MVD) increases from normal cervical tissue, through low- and high-grade CIN to SCC. We evaluated PD-ECGF immunoreactivity and correlated its expression with MVD in normal, premalignant, and malignant cervical tissue. PD-ECGF expression was assessed visually within the epithelial tissues and scored on the extent and intensity of staining. MVD was calculated by counting the number of vessels positive for von Willebrand factor per unit area subtending normal or CIN epithelium or within tumor hotspots for SCC. Cytoplasmic and/or nuclear PD-ECGF immunoreactivity was seen in normal epithelium. PD-ECGF expression significantly increased with histologic grade from normal, through low- and high-grade CIN, to SCC (P < .02). A progressive significant increase in the microvessel density was also seen, ranging from a mean of 28 vessels for normal tissue to 57 for SCC (P < .0005). No correlation was found between PD-ECGF expression and MVD (P = .45). We conclude that PD-ECGF expression and MVD increase as the cervix transforms from a normal to a malignant phenotype. PD-ECGF is thymidine phosphorylase, a key enzyme in the activation of fluoropyrimidines, including 5-fluorouracil. Evaluation of PD-ECGF thymidine phosphorylase expression may be important in designing future chemotherapeutic trials in cervical cancer.

Carcinoma, Squamous Cell↗
PubMed2000

Does histological incomplete excision of cervical intraepithelial neoplasia following large loop excision of transformation zone increase recurrence rates? A six year cytological follow up.

OBJECTIVE: To determine the risk of recurrent cervical intraepithelial neoplasia (CIN) in women with complete or incomplete excision of cervical intraepithelial neoplasia treated by large loop excision of transformation zone (LLETZ). DESIGN: A retrospective study SETTING: One consultant-led colposcopy clinic at Leicester Royal Infirmary POPULATION: Three hundred and ninety-four women referred consecutively to the colposcopy clinic between 1991 and 1992. MAIN OUTCOME MEASURES: The histological recurrence rate of CIN, length of cytological follow up following treatment related to degree of completeness of excision at initial treatment. RESULTS: Three hundred and twenty-two women had complete cytological or histological follow up. The mean length of follow up was 73 months with a mean number of six smears. Women with incomplete excision of CIN had a significantly higher risk of recurrent CIN (relative risk 8.23) occurring in a significantly shorter time compared with women with complete excision. CONCLUSIONS: This study demonstrates that large loop excision of transformation zone is successful in over 95% of cases. Cytological surveillance is satisfactory for follow up of women who have complete excision of CIN. Women with incomplete excision of CIN at initial LLETZ remain at significant risk of developing further CIN and long term colposcopic and cytological follow up is necessary.

Adolescent↗
PubMed2000

Trends in untreated caries in primary teeth of children 2 to 10 years old.

BACKGROUND: This article is the second in a series of three that focus on recent changes in the caries status of children and adolescents in the United States. METHODS: This study is based on analyses of data regarding untreated carious primary teeth among children 2 to 10 years of age from the first and third National Health and Nutrition Examination Surveys, or NHANES I and NHANES III. The NHANES is conducted periodically by the National Center for Health Statistics of the Centers for Disease Control and Prevention. RESULTS: Overall, the number of carious primary teeth among children 2 to 10 years old decreased from 1.42 as measured in NHANES I to 0.63 as measured in NHANES III. The number of carious primary teeth in children 2 to 10 years old also decreased across four demographic variables: age, sex, race and poverty level. CONCLUSIONS: The number of untreated carious primary teeth among children has declined. Since the 1970s, the absolute difference in untreated caries between disadvantaged children in the United States and the rest of the U.S. child population has narrowed, although not to the same extent as in permanent teeth. PRACTICE IMPLICATIONS: On average, children of preschool and elementary-school age have less untreated caries than in the past. More often, dentists do not need to treat on a first visit. This provides more opportunity to introduce these children to preventive dentistry at an early age.

Age Distribution↗
PubMed2000

Dentists' participation in capitation and preferred provider organization dental plans.

BACKGROUND: In 1998, the American Dental Association Survey Center conducted a telephone and mail survey of U.S dentists in private practice in an effort to determine the extent of dentists' participation in capitation and preferred provider organization, or PPO, dental plans and the characteristics of dentists who participate in those plans. METHODS: An initial phone screening survey was conducted with a random sample of 11,550 dentists in private practice. Dentists who indicated that they participated in capitation or PPO dental plans received a follow-up mail survey asking specific questions concerning these two types of dental plans. RESULTS: Almost one-half of responding dentists indicated that they participated in either capitation or PPO dental plans. However, far more dentists reported participating in PPO dental plans than in capitation dental plans. The majority of participating dentists' patients were reported to be fee-for-service patients. CONCLUSIONS: Dentists' participation in PPO dental plans generally increased from that indicated in previous surveys, though participation in capitation plans declined. There was some regional and demographic variation in participation in these dental plans, but such differences were not large. Pricing and concerns about quality of care continue to be the primary concerns of nonparticipating dentists. PRACTICE IMPLICATIONS: Dentists reporting participation in PPO dental plans are becoming more common, but such plans still do not cover the majority of participating dentists' patients. A large percentage of nonparticipating dentists cite pricing and concerns about quality care as reasons for not joining these plans.

American Dental Association↗
PubMed2000

Characteristics of dentists participating in capitation and Preferred Provider Organization dental plans.

BACKGROUND: In 1998, the American Dental Association Survey Center conducted a telephone and mail survey of U.S. dentists in private practice in an effort to determine the extent of dentists' participation in capitation and preferred provider organization, or PPO, dental plans and the characteristics of dentists who participate in those plans. METHODS: An initial telephone screening survey of a random sample of 11,550 dentists in private practice was conducted to identify dentists who participated in PPO or capitation dental plans. Dentists who participated in either of these plan types then were asked to complete a mail survey on their plan participation. RESULTS: The majority of dentists participating in either type of dental plan reported having never left a dental plan. Dentists who belonged to more than one PPO or capitation plan reported that a larger percentage of their patients were enrolled in these plans and that more of their practice's gross income came from the plans. Participation in PPO and capitation plans has had a positive impact on the practices of many of the responding dentists, particularly with regard to expanding their patient base. CONCLUSIONS: The authors found that the majority of dentists participating in PPO dental plans found it to be a positive experience overall. Dentists participating in capitation plans were less satisfied; more than 50 percent of capitation plan participants reported some level of dissatisfaction with the plans. The majority of dentists participating in a PPO plan expected to renew participation when their current contract expired; a much smaller percentage (though still a majority) of responding capitation-plan participants indicated the same. PRACTICE IMPLICATIONS: Responding dentists' overall indication of satisfaction with their current PPO plan participation probably indicates further growth for these dental plans. On the other hand, capitation plan participants seem much less satisfied with their plans. PPO plans, therefore, seem much more likely to be the type of plan that dentists will choose in the future.

Capitation Fee↗
PubMed2000

Selling your practice at retirement. Are there problems ahead?

BACKGROUND: The dental work force is maturing as fewer dentists enter practice. In this article, the authors considered two questions: "Will demographic trends in the numbers of dentists leaving and entering practice place additional downward pressure on the value of dental practices?" and "How important is the sale of practices for retirement income?" METHODS: To address the first question, the authors estimated the number of retirees using 62 years as retirement age, and they projected the number of graduates using current trends of first-year enrollments. To address the second question, the authors used the ADA's 1995 Survey of Current Issues in Dentistry, which addressed dentists' retirement savings. RESULTS: The annual rate of dentists' retiring is projected to be 2.1 percent compared with 1 percent among dentists projected to graduate during the period of 2001-2020. Although dental practice value is 40 percent or more of practitioners' reported retirement savings, the majority of dentists report that they do not depend on the sale of their practices to finance their retirement. CONCLUSIONS: In the next 20 years, the number of retirees will grow faster than the number of graduates, exerting a downward pressure on the value of dental practices. PRACTICE IMPLICATIONS: To successfully plan for retirement, dentists need to carefully assess their target levels of retirement savings, the time of their retirement and their dependence on the sales of their practices.

Adult↗
PubMed2000

Racial/ethnic variations of practicing dentists.

BACKGROUND: In recent years, the dental school population has changed from being predominantly white male to a more diverse racial and ethnic makeup. Noting this change in the student population, the American Dental Association undertook an in-depth study of the various racial/ethnic groups. METHODS: Questionnaires were sent to approximately 8,000 dentists nationwide. Samples were drawn for each of the following racial/ethnic groupings: white, black, Hispanic, Native American and Asian. The survey instrument asked questions about personal characteristics, work and private practice issues, household and practice income, and patient characteristics; it also asked for dentists' opinions. A final adjusted response rate of 57.0 percent was achieved. RESULTS: The majority of all dentists responded that they were "very satisfied" with their profession, but the survey found variations in patient mix, employment history and provision of free or discounted care. CONCLUSIONS: The survey examined dentists by race/ethnicity to identify differences and similarities. Cultural and ethnic minorities are the fastest growing segment of the U.S. population. As the profession becomes more diverse, practice patterns will affect the overall dental profession. PRACTICE IMPLICATIONS: Dentists' racial/ethnic backgrounds may change the provision of care as patient mix varies, with each dentist group treating a specific group of patients in regard to family income, racial/ethnic background and subgroups for whom they offer free or reduced-rate dental care.

Career Mobility↗